We demonstrated previously (S. Kawamura et al., Int. J. Cancer, 94: 343-347, 2001) that large amounts of ganglioside GM3 accumulate in superficial bladder tumor, compared with invasive bladder tumors and that exogenous GM3 inhibits the invasive potential of bladder tumor cells. To apply the GM3 overexpression system to bladder tumor therapy, direct evidence for the important role of GM3 in bladder tumor invasion must be obtained through transfer of the gene responsible for GM3 overexpression. To determine the most appropriate cancer cell line for elucidating the antitumor effect of ganglioside GM3 overexpression, the present study examined glycolipid composition, enzyme activity, and mRNA expression of the glycosyltransferases responsible for GM3 synthesis in the bladder tumor cell lines KK-47, J82, MGH-UI, YTS-1, and MBT-2. A murine bladder carcinoma cell line (MBT-2) was transfected with a GM3 synthase [(lactosylceramide α2,3-N-acetyl sialic acid transferase); sialyltransferase-I; SAT-I] cDNA, because this line does not naturally express GM3. Stable transfectants (MBT-2-SAT-I) that overexpressed GM3 were characterized by a reduced potential for cell proliferation, motility, invasion, and xenograft tumor growth, and an increase in the number of apoptotic cells. In the proportion of synthetic S phase, cells did not differ between MBT-2-SAT-I and mock-transfectant cells. These results suggest that the decreased proliferative potential related to GM3 overexpression was attributable to the increased number of apoptotic cells. Although details of the mechanism of apoptosis remain unclear, the overexpression of GM3 by gene transfer of SAT-I may present a novel therapeutic modality.
|Number of pages||5|
|Publication status||Published - 2002 Jul 1|
ASJC Scopus subject areas
- Cancer Research